Nykode Therapeutics Asa · OSL:NYKD
Nykode Therapeutics Asa — Investor Day (May 2022)
79 slides from Nykode Therapeutics Asa's investor day presentation, May 12, 2022
Slide 1: Capital Markets Day
Capital Markets Day May 12, 2022
Slide 2: Forward-looking statement
Forward-looking statement This announcement and any materials distributed in connection with this presentation may contain certain forward- looking statements. By their nature, forward-looking statements involve risk and uncertainty because they reflect the company’s current expectations and assumpt
Slide 3: Today's presenters from Nykode management and Oslo University Hospital
Today’s presenters from Nykode management; and Oslo University Hospital MICHAEL ENGSIG AGNETE FREDRIKSEN SIRI TORHAUG MIKKEL W. PEDERSEN HARALD GURVIN KRISTINA LINDEMANN Chief Executive Chief Innovation & Chief Medical Officer Chief Scientific Officer Chief Financial M.D., Ph.D. Officer Strategy Off
Slide 4: Agenda
Agenda Business status and journey 01 05 Business development and partnering strategy Innovation strategy Capital Markets Strategy, 02 06 Financials and upcoming events Pipeline update Q&A 03 07 Research update 04 Nykode Therapeutics | Capital Markets Day | Non-Confidential 4
Slide 5: Business status and journey
01 Business status and journey Another transformational year 5
Slide 6: Pipeline
Pipeline Discovery/ Upcoming Program Indication Phase 1 Phase 2 Phase 3 Partnerships Preclinical Milestones Nykode 1H23: VB10.16 (off-the-shelf) HPV16+ cervical cancer3 3 Updated data Oncology Internal (off-the-shelf) Undisclosed targets 4 VB10.COV2 SARS-CoV-2 2H22: Interim Infectious data Disease I
Slide 7: Top-tier collaborations for cancer and infectious disease vaccines
Top-tier collaborations for cancer and infectious disease vaccines valued potentially more than $1.64 billion plus royalties Partner Collaboration Terms Clinical Development $925M~ Regeneron to develop and potentially Multi-target license and $30M upfront commercialize products collaboration agree
Slide 8: Continued strong growth across the organization
Continued strong growth across the organization Number of employees Strong focus on R&D Geographical footprint 150 12,7% 142 125 100 102 14,8% Norway (HQ) 118 (83%) 75 52,8% Denmark 24 (17%) 51 50 19,7% Total 142 24 25 0 2019 2020 2021 2022 Dec 31 Dec 31 Dec 31 May 12 Research Medical CMC Other Nyko
Slide 9: New flagship lab opened in Oslo Science City
New flagship lab opened in Oslo Science City The heart of Nykode’s innovation power-house • Vaccine discovery • Platform improvements and next generation products • Process, analytical and formulation development • Immune monitoring for clinical trials (GCLP) Nykode Therapeutics | Capital Markets Da
Slide 10: Strengthening the Nykode leadership team
Strengthening the Nykode leadership team HARALD GURVIN, CFO MIKKEL W. PEDERSEN, CSO ELISE RAMSE, CHRO PETER FATUM, HEAD OF QA • Long career in the field • More than 15 years • Extensive experience • More than 25 years of of finance experience with bio- with HR and experience from the • CFO at Flex L
Slide 11: Added strong industry experience to the Board of Directors
Added strong industry experience to the Board of Directors MARTIN NICKLASSON, BIRGITTE VOLCK, MEMBER OF THE CHAIR OF THE BOARD AND CHAIR OF BOARD AND • Executive level, drug REMUNERATION COMMITTEE CO-CHAIR OF R&D COMMITTEE development experience Currently, serves as: Currently serves as: • Chair of
Slide 12: Continuing the internationalization with two new members
Continuing the internationalization with two new members ELAINE SULLIVAN ANNE WHITAKER • International executive level, Currently, serves as: Currently serves as: • Drug development • CEO of Keltic Pharma Therapeutics Ltd • Chairman of Aerami Therapeutics, Inc. and • Various Non-executive directorsh
Slide 13: Proven Strategy to Generate First-in-Class Immunotherapies and Create Shareholder Value
Proven Strategy to Generate First-in-Class Immunotherapies and Create Shareholder Value VISION STRONG VALIDATING PARTNERSHIPS To build the leading immunotherapy company Potentially > $1.64B in payments + royalties developing game changing medicine across an from top-tier partners Regeneron, Gene
Slide 14: Innovation strategy
02 Innovation strategy 14
Slide 15: Nykode's innovation strategy
Nykode’s innovation strategy The Innovation Strategy encapsulates our vision of finding new ways of coding medicine by breaking down conventional drug design Creating novel differentiated platform technologies applicable to fuel multiple products and optimize value-creation Coding novel medicines CO
Slide 16: Pipeline update
03 Pipeline update 16
Slide 17: Nykode development pipeline
Nykode development pipeline Clinical platform exposure EU & US exposure ❑ Favorable safety profile – well tolerated as mono- and 5 clinical trials combination therapy 8 countries 4 different compounds ❑ Correlation of immune responses and clinical efficacy 12 different indications >150 subjects ❑ Cl
Slide 18: VB10.NEO
VB10.NEO 18
Slide 19: VB10.NEO: Exclusively Licensed to Genentech
VB10.NEO: Exclusively Licensed to Genentech Global, oncology collaboration between Nykode and Genentech to develop individualized neoantigen cancer vaccines across multiple tumor types Conduct clinical Phase1b Responsible, and bear all trial testing 2 dose levels of costs, for all further clinical,
Slide 20: VB10.NEO: Individualized cancer DNA vaccine against various solid tumor types
VB10.NEO: Individualized cancer DNA vaccine against various solid tumor types with locally advanced or metastatic disease Individualized treatment with broad potential across solid tumor indications VB N-02: collaboration project with Genentech N-01 N-02 ◆Phase 1/2a trial with ◆Dose escalation, phas
Slide 21: VB N-01: Trial design facilitates efficacy readouts in each patient
VB N-01: Trial design facilitates efficacy readouts in each patient Signs of clinical efficacy correlated with strong dominant CD8 immune responses Neoepitope-specific CD8 dominating CHART 1 STABLE DISEASE AT VACCINATION START immune responses in SCCHN patients N with clinical response Marked chan
Slide 22: Interim results of VB C-02 trial in cervical cancer
Interim results of VB C-02 trial in cervical cancer Kristina Lindemann, MD, PhD Associate Professor Senior consultant/Head of Research Department of Gynecologic Cancer Oslo University Hospital – Radiumhospital Oslo, Norway 22
Slide 23: Kristina Lindemann – potential conflicts of interest
Kristina Lindemann – potential conflicts of interest • Personal financial interests • GSK – Speaker • MSD – Advisory board • Eisai – Advisory board • Institutional financial interests • GSK – Study support • AstraZeneca – Study support / Consultancy • MSD – Study support / Advisory board • Roche – S
Slide 24: Cervical cancer
Cervical cancer A leading cause of cancer death in women worldwide Cervical cancer is the fourth leading cause of cancer death in women worldwide Each year nearly 600,000 women are diagnosed with cervical cancer worldwide Cervical cancer is often curable when detected early, but treatment opti
Slide 25: Advanced cervical cancer
Advanced cervical cancer Limited treatment options after progression on first-line treatment Pembrolizumab is the only anti–PD-1 agent approved in the US as second-line therapy for patients with PD-L1 positive recurrent or metastatic cervical cancer High unmet medical need US approval based on KEY
Slide 26: HPV16 is an ideal target for off-the-shelf cancer vaccines
HPV16 is an ideal target for off-the-shelf cancer vaccines High-grade cervical intraepithelial neoplasia (CIN) caused by infection with human papillomavirus (HPV) often precedes the development of cervical cancer Almost all cervical cancers are caused by HPV infection and HPV16 accounts for more
Slide 27: VB C-01: VB10.16 monotherapy in pre-cancerous cervical lesions
VB C-01: VB10.16 monotherapy in pre-cancerous cervical lesions: strong signs of vaccine-induced clinical efficacy Highly significant correlation Lesion size reduction in all patients in PD-L1 was upregulated in post- between vaccine-induced T cell expansion cohort followed >4 months vaccination lesi
Slide 28: VB C-02: VB10.16 in combination with atezolizumab in advanced cervical cancer
VB C-02: VB10.16 in combination with atezolizumab in advanced cervical cancer A Multi-Centre, Single Arm, Open-label Phase 2a Trial of the Combination of VB10.16 and atezolizumab in Patients with Advanced or Recurrent, Non-resectable HPV16 Positive Cervical Cancer (NCT04405349) Objectives: safety/
Slide 29: Interim analysis
Interim analysis Number of patients included in the pre-planned interim analysis Population N Enrolled patients 50 Efficacy Analysis Set (EAS) 39 At least one available post-baseline scan at cut off date* Completed Treatment 6 Discontinued 21 Ongoing 12 Safety Analysis Set (SAS) 50 At least one dose
Slide 30: Baseline characteristics of EAS population
Baseline characteristics of EAS population C-02 included a heavily pre-treated population with advanced cervical cancer Characteristic N (%) Characteristic N (%) Age (mean) 48.9 yrs ECOG Age (median) 47.0 yrs 0 22 (56%) Ethnicity (White) 39 (100%) 1 17 (44%) Prior systemic treatment lines PD-L1 stat
Slide 31: Best overall response by blinded independent central review
Best overall response by blinded independent central review Promising clinical activity in majority of patients with advanced cervical cancer including PD-L1 negative patients BOR rate N (%) Complete Response 2 (5%) ORR = 21% (8/39 patients) Partial Response 6 (15%) DCR = 64% (25/39 patients) Stable
Slide 32: Anti-tumor activity was observed in majority of patients
Anti-tumor activity was observed in majority of patients including 9 patients with SD+ 1 0 0 Best Overall Response % change lesion size 5 0 20 0 -30 -5 0 N=38 1 NE; not evaluable -1 0 0 SD+ = SD with shrinkage in target lesion(s) Nykode Therapeutics | Capital Markets Day 2022 | Non-confidential 32
Slide 33: Anti-tumor activity in patients with positive and negative baseline PD-L1 status
Anti-tumor activity was observed both in patients with positive and negative baseline PD-L1 status Tumor regression in PD-L1 +/- 1 0 0 PD-L1 pos PD-L1 ORR (n/N) DCR (n/N) PD-L1 neg status 5 0 % change lesion size 20 Positive 27% (6/22) 77% (17/22) 0 (TIC 1-2) -30 -5 0 Negative N=33 17% (2/12) 58% (7
Slide 34: Promising efficacy with durable responses
VB10.16 in combination with atezolizumab showed promising efficacy with durable responses 100 Complete/Partial Response Stable Disease Progressive Disease % change lesion size 50 20 0 • Durable responses in the DCR population 30 • 6 out of 8 ORR patients -50 have an ongoing response -100 0 3 6 9 12
Slide 35: Safety and tolerability
Safety and tolerability VB10.16 was generally well-tolerated and has a favorable safety profile TRAEs considered related to VB10.16 System Organ Class Any Grade 3 Grade 4-5 Preferred Term Grade N=50 (%) N=50 (%) VB10.16 in combination with atezolizumab was N=50 (%) generally well-tolerated All TRAEs
Slide 36: Patient case: T cell excluded and PD-L1 negative tumor with clinical response
Patient case 1 T cell excluded and PD-L1 negative tumor with clinical response Patient T cells present in Shrinkage of target lesion 66 years old female with squamous cell cervical stroma, but excluded (retrocaval lymph node) carcinoma – diagnosed in November 2019 and from the tumor area enrolled in
Slide 37: Patient case: Deepening and durable clinical response
Patient case 2 Deepening and durable clinical response Patient T cells present in 55 years old female with squamous cell Shrinkage of target lesions tumor tissue cervical carcinoma – diagnosed in November (pelvic lymph node) CD3+CD8+Ki67+ 2019 and enrolled in August 2021 with progression after radio
Slide 38: VB C-02 Interim Analysis – Conclusion
VB C-02 Interim Analysis – Conclusion VB10.16 in combination with atezolizumab showed promising efficacy in heavily pre-treated patients with advanced HPV16+ cervical cancer who have a high unmet medical need VB10.16 in combination with atezolizumab showed durable responses with a very high DCR
Slide 39: VB10.16: Therapeutic cancer DNA vaccine against HPV16 induced pre-malignancies and malignancies
VB10.16: Therapeutic cancer DNA vaccine against HPV16 induced pre-malignancies and malignancies Expanding the clinical development into multiple indications VB10.16 Off the shelf vaccine targeting foreign viral antigens C-01 C-02 C-03 HPV16+ Pre- Advanced HPV16+ HPV16+ Head & Neck cancerous cervical
Slide 40: C-03: Phase 1b dose finding trial in HPV16-positive head and neck cancer
C-03 NYK003-C-03: A Phase 1b, Open Label, Dose Finding Trial to Evaluate Safety, Immunogenicity and Anti-Tumor Activity of VB10.16 in Combination with CPI in Subjects with HPV16-positive Head and Neck Squamous Cell Carcinoma
Slide 41: HPV16-positive squamous cell head and neck cancer
HPV16-positive squamous cell head and neck cancer Continued increase in cases worldwide • The number of patients with squamous cell head and neck cancer (HNSCC) has risen substantially during the last decades and around 560,000 patients are now diagnosed yearly • This rising incidence in HNSCC is ma
Slide 42: NYK003-C-03 Phase 1b trial combining VB10.16 with a checkpoint inhibitor
NYK003-C-03 Phase 1b trial Combining VB10.16 with a checkpoint inhibitor (CPI) • The use of immunotherapy is currently limited to PD-L1+ recurrent or metastatic advanced HNSCC • Responses to immunotherapy in this advanced setting are limited with modest response rates (ORR ranging from 13-17%) • Nyk
Slide 43: VB10.COV2
VB10.COV2 Capital Market Day 2022 | Non-confidential 43
Slide 44: SARS COV2: A continuous global health threat
SARS COV2: A continuous global health threat Need for new vaccine approaches With SARS CoV2 a new global Covid -19 will become a human pathogen has emerged. It disease that health systems will need to manage on an will stay with us and has to be ongoing base* addressed by health systems globally SAR
Slide 45: Phase 1/2 trial investigating two candidates as a diverse booster
Phase 1/2 trial investigating two candidates as a diverse booster in previously vaccinated subjects A Phase 1/2, open label, dose VB-D-01 TRIAL DESIGN escalation trial with two SARS- CoV-2 virus vaccine candidates (C1) and (C2) «RBD» CANDIDATE Candidate 1: Healthy Cohort 1: Cohort 2: C1: First s
Slide 46: T-cell vaccine rationale
T-cell vaccine rationale Future VOCs are not COVID-19 vaccines inducing a unilaterally likely to be milder broader T cell immunity across or cause a lower disease populations may therefore be Engaging FDA to ensure T-cell burden a good way to prevent severe measurements into COVID disease across fut
Slide 47: Research update
04 Research update 47
Slide 48: Agenda
Agenda Discovery pipeline update Platform improvement strategy Tolerizing vaccines Nykode Therapeutics | Capital Markets Day | Non-Confidential 48
Slide 49: Discovery pipeline update
b> nykode therapeutics Discovery pipeline ate
Slide 50: Discovery pipeline
Discovery pipeline Upcoming Program Indication Early Discovery Late discovery Pre-clinical Phase 1 Partnerships Milestones Oncology Off the shelf – Regeneron program 1 Regeneron6 – Regeneron program 2 Regeneron6 – Regeneron program 3 Regeneron6 NYK011 Undisclosed target Selection of lead Infectious
Slide 51: Regeneron collaboration
Regeneron collaboration Multitarget collaboration with the aim of using Nykode’s modular vaccine platform combined with Regeneron’s unique antigen selection expertise to discover and develop • Two vaccine programs within infectious diseases • Three vaccine programs within oncology The collaboration
Slide 52: Platform improvement strategy
Platform improvement strategy
Slide 53: Preambles to technology platform improvement
Preambles to technology platform improvement • Nykode’s pipeline as of today consists of infectious disease and cancer vaccines, which are based on the VaccibodyTM platform • The ability of the Vaccibody platform to induce T cell responses is well proven in preclinical as well as clinical studies •
Slide 54: DNA platform provides near endless opportunities
DNA platform provides near endless opportunities • 2022 (F) Global therapeutic protein sales • Modular and flexible antigen presenting cell ~USD 300 Billion1 targeted vaccines • In situ production of recombinant • Clinically proven technology for therapeutic proteins highly attractive inducing T cel
Slide 55: Why DNA and not RNA?
Why DNA and not RNA? The “success” of the COVID19 vaccines have glorified mRNA technologies but significant challenges remain • Unspecific delivery of the mRNA may cause unwanted inflammation as seen in e.g., heart muscle in younger males1 • mRNA together with key LPN constituents stimulates IL1-bet
Slide 56: Four-pillar platform improvement strategy
Four-pillar platform improvement strategy Construct quality Non-vaccines Focusing on the quality of vaccine candidates Explore opportunities for delivering non-vaccine proteins using the DNA platform Dose and delivery* Novel vaccine formats Explore and optimize dose, plasmid size Develop novel forma
Slide 57: Focus of today will be novel vaccine formats
Focus of today will be novel vaccine formats Novel vaccine formats Develop novel formats with optimized and directed immune responses Nykode Therapeutics | Capital Markets Day | Non-Confidential 57
Slide 58: Numerous new codes designed and evaluated experimentally
Numerous new codes designed and evaluated experimentally Targeting unit • Targeting of multiple different receptors on different APCs • Multiple natural ligands and antibody like molecules Dimerization unit • Several new designs • Smaller units, more units Antigenic unit • Combinations of structured
Slide 59: 4th Module: Adding gas pedal, brake and/or steering wheel
4th Module Adding gas pedal, brake and/or steering wheel 1 DNA Vaccibody 2 4 3 + A 4th module DNA is inserted into the plasmid 4th module • May encode any immune enhancing, immune inhibiting and/or immune guiding polypeptide + • Ribosome skipping sequence ensures 5th module assembly and secretion of
Slide 60: 4th module has no impact on secretion of the Vaccibody
4th module has no impact on secretion of the Vaccibody 4TH MODULE HAS NO IMPACT ON 4TH MODULE CYTOKINE HIGHLY SECRETED 4TH MODULE CYTOKINE VACCIBODY SECRETION SECRETED BINDS TO TARGET RECEPTOR 5 4 2.0 α-4th module cytokine 4 3 1.5 OD450nm OD450nm OD450nm 3 2 1.0 2 1 0.5 1 αCH3 0 0 0.0 VB+4th module
Slide 61: 4th module cytokine boosts T cell and anti-tumor responses
4th module cytokine boosts T cell and anti-tumor responses driven by a tumor specific antigen vaccine VB-CT26-GM CT26 tumor model Tumor size (cm3) VB-CT26-GM VB-CT26 GM-CSF VB-core CD24+ DCs in muscle cDC1 in muscle moDCs in muscle 1.5×10 4 1.5×10 4 1.5×10 4 VB-CT26-GM VB-CT26-GM VB-CT26 VB-CT26 Cel
Slide 62: 4th module cytokines boost T cell and antibody responses to SARS-COV-2 vaccine
4th module cytokines boost T cell and antibodies responses induced by a SARS-COV-2 subunit vaccine VB-COV2 Antibody VACCINE INDUCED responses ANTIBODY RESPONSES T cell VACCINE INDUCED IFNresponses g T CELL RESPONSES RBD RBD RBD RBD + VB-core VB-core VB-COV2+GM VB-COV2+GM VB-COV2 VB-COV2 VB-COV2-Cyt3
Slide 63: 4th module summary and perspectives
4th module summary and perspectives The 4th module platform allows Nykode to introduce additional new DNA codes to our vaccines with the purpose of boosting or directing the immune responses • 4th module DNA codes do not impact production of the Vaccibody protein • 4th module encoded cytokines boost
Slide 64: Tolerizing vaccines
a nykode therapeutics Tolerizing vaccines ———
Slide 65: Two key therapeutic areas and a third for future growth
Two key therapeutic areas and a third for future growth 1 Oncology 2 Infectious disease 3 Tolerance Nykode Therapeutics | Capital Markets Day | Non-Confidential 65
Slide 66: Preambles for tolerizing vaccines
Preambles for tolerizing vaccines Antigen-specific tolerization for the treatment of auto-immune diseases has the potential to blunt autoimmunity without compromising normal immune function Various approaches have been pursued including delivery of auto- immune antigens by means of DNA, peptides or
Slide 67: Shifting the balance of the immune system
Shifting the balance of the immune system T regulatory T effector cells T regulatory T effector cells T effector cells cells T regulatory cells cells Disruption of Balance Balanced immune system Disruption of Balance Autoimmune disorders Normal situation Cancer Tolerizing vaccines should shift the b
Slide 68: Platform technology offers unique possibilities to explore Ag-specific immune tolerance
Nykode’s platform technology offers unique possibilities to explore Ag-specific immune tolerance CANCER AND INFECTIOUS DISEASE AUTOIMMUNITY, ALLERGY ETC Stimulatory Tolerogenic DC DC Natural ligands or scFv binding diverse set of surface receptors IL-12, IFNγ, TNFα, IFNα, IL-6 IL-10, TGFβ, IDO, PD-1
Slide 69: Multiple sclerosis as model system
Multiple sclerosis as model system Multiple sclerosis (MS) Chronic autoimmune disease of the central nervous system (CNS), where the myelinated axons in the CNS are destroyed Animal model system Multiple sclerosis Experimental autoimmune encephalomyelitis (EAE) is a clinically relevant animal mo
Slide 70: Exploratory vaccine construct induces proliferation of MOG specific T regulatory cells
Exploratory vaccine construct induces proliferation of MOG specific T regulatory cells Tolerizing vaccine design T-VB-MOG-1 Targeting specific receptor on tolerizing antigen presenting cells MOG immunogen T-reg cells Proliferating T-reg cells 4 25 30 4th module immune inhibitory cytokine ✱✱ IL
Slide 71: What is next for tolerizing vaccines?
What is next for tolerizing vaccines? Initial data with the various tolerizing vaccine constructs are encouraging • Increases in antigen specific T regulatory cells • A shift in the cytokine balance towards an immune suppressive profile Patent applications filed to protect the overall concepts Addit
Slide 72: Business development strategy
05 Business development strategy 72
Slide 73: Nykode has entered key partnership deals with top-tier biopharma partners
Nykode has entered 3 key partnership deals with top-tier biopharma partners since Q4 2020 2020: Out-licensing individualized cancer vaccine at clinical stage to leverage Genentech’s knowledge and capabilities to accelerate program to market 2021: In-licensing clinically validated antigens to acceler
Slide 74: Nykode's business development strategy
Nykode’s business development strategy MAXIMIZING VALUE BY STRENGTHENING THE PLATFORM AND ACCELERATE PRODUCTS THROUGH PARTNERSHIPS + Seek partners accessing • Antigens • Combination therapies • Technologies + Seek partners with expertise that accelerate our programs Antigen Shared antigen Multiple o
Slide 75: Capital Markets Strategy, Financials and upcoming events
06 Capital Markets Strategy, Financials and upcoming events 75
Slide 76: Capital Markets Strategy
Capital Markets Strategy UPLIFT ON OSLO STOCK EXCHANGE POTENTIAL INTERNATIONAL LISTING Initiated process for transfer of Continues to explore a potential listing of shares from Euronext listing on Nasdaq Global Growth to the main market of Markets in the U.S. over the the Oslo Stock Exchange lon
Slide 77: Strong financial foundation for achieving our vision
Strong financial foundation for achieving our vision Financially well positioned to grow and execute the ompany’s strategy over the next years Strong balance sheet YE 2021 liquidity of $228 million Milestone payment of $20 million for initiation of Phase 1b trial in 2H 2021 received 1Q 2022
Slide 78: Upcoming Catalysts
Upcoming Catalysts 2022 Key Priorities Program Indication Partnerships Milestones Wholly-Owned Candidates* ✓ Phase 2 interim data • Advance internal oncology VB10.16 programs including cervical HPV16+ cervical cancer (off-the-shelf) • Updated development strategy cancer program Oncology • Updated Ph
Slide 79: Q&A
Q&A Unlocking the future of medicine Contact: Nykode NykodeTherapeutics | Capital Therapeutics | Markets Day | Non-Confidential IR@nykode.com